The long-term goal of this proposal is to determine, at the cellular level, how different extrinsic modulatory inputs select distinct motor patterns from multifunctional neural networks that underlie behavior. In all animals, neuromodulation enables single motor circuits to produce many different activity patterns, thereby producing distinct behaviors. The multifunctional character of such networks derives largely from the actions of modulatory transmitters which alter the cellular and synaptic properties of neurons. These substances are released by sensory, humoral and projection neurons to influence these networks. Thus far, little is known about how specific extrinsic modulatory pathwaysselect a particular motor pattern from a multifunctional network. This issue will be addressed using a well-defined model system, the isolated crabstomatogastric nervous system, in which all of the relevant neurons, synapses and membrane properties can be identified and manipulated. Specifically, (1) the distinct chewing motor pattern triggered by a newly identified extrinsic modulatory pathway will be characterized and compared with the patterns elicited by two previously studied sensory pathways. (2) This will include identifying the intervening projection neurons that mediate this action, including the underlying cellular and synaptic mechanisms. This will help establish a new cellular-level model regarding whether distinct extrinsic inputs elicit different motor outputs from the same network by activating the same, overlapping or different sets of projection neurons. (3) The state-dependent and state- independent consequences from the overlapping or sequential activation of distinct extrinsic inputs will also be determined, as will (4) the roles played by distinct co-releasedtransmitters in these processes. This proposal aims to combine cellular neurophysiological, pharmacological and anatomical approaches to elucidate general principles about motor pattern selection from multifunctional networks. This will guide comparable studies in the more complex and less accessible mammalian nervous system. Because the same organizing principles underlie network activity in all animals, this work will also facilitate a better understanding of network dysfunction that produces aberrant or loss of behavior, such as occurs as a consequence of spinal cord injury, stroke or altered modulatory states such as after drug addiction.